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Appearance of Far Peripheral Retina in Normal Eyes by Ultra-widefield Fluorescein Angiography
Accepted Manuscript Appearance of far peripheral retina in normal eyes by ultra-widefield fluorescein angiography Jing Lu, Guiying Mai, Yan Luo, Mei Li, Di Cao, Xiao Wang, Hong Yan, SriniVas R. Sadda, Lin Lu PII:
S0002-9394(16)30480-9
DOI:
10.1016/j.ajo.2016.09.024
Reference:
AJOPHT 9906
To appear in:
American Journal of Ophthalmology
Received Date: 17 May 2016 Revised Date:
17 September 2016
Accepted Date: 21 September 2016
Please cite this article as: Lu J, Mai G, Luo Y, Li M, Cao D, Wang X, Yan H, Sadda SR, Lu L, Appearance of far peripheral retina in normal eyes by ultra-widefield fluorescein angiography, American Journal of Ophthalmology (2016), doi: 10.1016/j.ajo.2016.09.024. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Abstract
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PURPOSE: To characterize the appearance of the far peripheral retina of normal eyes using ultra-widefield fluorescein angiography (UWFA). DESIGN: Cross-sectional study. METHODS: This study enrolled 101 eyes with best corrected visual acuity ≥ 20/20, refractive error < 3.00D, and without visible retinal pathologic changes under a slit lamp–based condensing lens. The far peripheral retina was detected by UWFA. Ciliary body thickness (CBT) at 3 mm (CBT1) and 2 mm (CBT2) posterior to the scleral spur was measured by ultrasound biomicroscopy. RESULTS: In the far peripheral retina, granular background fluorescence (GB) appeared in all eyes (100%), a mottled fluorescent band (MB) appeared in 44 (43.6%) eyes, and retinal vascular leakage (VL) appeared in 20 (19.8%) eyes. According to peripheral angiographic findings, the eyes were allocated into three groups: group 1 (MB- and VL-), group 2 (MB+ and VL-), and group 3 (MB-/+ and VL+). Ultrasound biomicroscopy showed ciliary body edema and exudates in group 3. The mean CBT1 (mm) and CBT2 (mm) of group 3 were greater than those of group 1 and group 2 (0.315 ± 0.037 vs. 0.240 ± 0.019 vs. 0.251 ± 0.030; 0.571 ± 0.084 vs. 0.375 ± 0.051 vs. 0.410 ± 0.050, P = .000 for both CBT1 and CBT2). The mean CBT1 and CBT2 showed no difference between group 1 and group 2 (P = .575 for CBT1; P = .150 for CBT2). CONCLUSIONS: Normal peripheral retinas generally show granular background fluorescence, with or without a mottled fluorescent band.
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Appearance of far peripheral retina in normal eyes by ultra-widefield fluorescein angiography Jing Lu1, Guiying Mai1, Yan Luo1, Mei Li1, Di Cao1, Xiao Wang1, Hong Yan1, SriniVas R. Sadda2, Lin Lu1
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1. State Key Laboratory of Ophthalmology, Image Reading Center, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China 2. Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California, USA
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Corresponding author: Lin Lu, State Key Laboratory of Ophthalmology, Image Reading Center, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China; phone: +86 13809773029; fax: 86-20-87335931; e-mail: [email protected]
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Short title: Peripheral retina by ultra-widefield fluorescein angiography
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Fundus fluorescein angiography (FA) has been used in pathophysiological evaluation of the retina and the choroid for more than 50 years.1 As the traditional fundus camera for FA can only offer a 30–60° view field of the fundus in a single shot, the seven-standard field protocol and the nine-field protocol have been developed to increase the view field of FA.2, 3 However, they are technically challenging for both patients and photographers, and fail to image the far peripheral retina. The subsequent application of a confocal scanning laser ophthalmoscope with a Staurenghi contact lens expands the viewing capability to a 150° view field, while its contact nature makes it less preferable in clinical application. The advent of the noncontact Optos C200 MA ultra-widefield retinal imaging system (Optos PLC, Dunfermline, Scotland, UK) makes it possible to observe the far peripheral retina via FA imaging in a variety of fundus diseases.4, 5 The Optos system is convenient to operate with extremely widefield visualization, and its newly commercial device has established a built-in stereographic projection software to reduce distortion.6 More recently, Heidelberg Engineering (Heidelberg, Germany) has developed a noncontact ultra-widefield fluorescein angiography (UWFA) imaging module that captures a 102° view field of the fundus in a singl e image.7 Although not used as widely as the Optos now, the ultra-widefield imaging lens offers the advantage of easy interchange with other existing lenses. It has been used successfully to inspect infants’ retinas intraoperatively.8 In our clinical practice, a mottled fluorescent band is frequently observed near the ora serrata in FA images. Whether this mottled fluorescent band is normal has not been confirmed yet. Only a few articles have been focused on the peripheral retina in normal eyes. One recent study has quantitatively evaluated the area of normal perfused retina in UWFA images.6 Another study has estimated the normal distance from vascular termini to ora serrata in children’s eyes.9 These studies has given detailed analysis of the perfusion and nonperfusion status of the peripheral retina, but still leaving other UWFA image features of the normal far peripheral retina undescribed. Therefore, our study aimed to investigate the appearance of the far peripheral retina in normal eyes by using the Heidelberg Spectralis UWFA imaging system. Such a description will provide valuable normative data for understanding pathologies of the far peripheral retina showing by FA images.
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METHODS This cross-sectional study was conducted from November 2014 to January 2016 at the fundus outpatient clinic in Zhongshan ophthalmic center. The study adhered to the tenets of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Zhongshan Ophthalmic Center, Sun Yat-Sen University (IRB approval number: 2016KYPJ029) and registered in ClinicalTrials.gov (ID number: NCT02856139). Informed consent for the study was obtained from each subject at the time of enrollment. Subjects All patients underwent a comprehensive eye examination including slit-lamp biomicroscopy, tonometry, refractive error measurements, and dilated fundus examination with a slit lamp–based +78 D or +90 D lens. Both eyes of patients with merely floaters or the fellow eyes of patients with retinal vein occlusion (RVO) or central serous chorioretinopathy (CSC) without any ocular pathologic findings in the above
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mentioned preliminary examinations were included in the study. Subjects with a history of ocular surgery, best-corrected visual acuity < 1.0 (20/20), refractive error ≥ 3.00 D, presence of ocular or systemic diseases, or opacity of refractive media which interfered with the peripheral retina image quality, were excluded from this study. Eyes were excluded if the quality of their FA images prevented reliable evaluation. The prevalence of symptomatic10 and asymptomatic floaters11 are fairly common in the general population and floaters cannot be considered abnormal when lacking other pathologic findings. Therefore, the eyes with floaters but without other pathologic findings in our study were set as “normal eyes” to investigate the appearance of the far peripheral retina. Demographic and clinical data such as age, gender, and reasons for undergoing FA were collected. All fundus examinations including FA were evaluated independently by two masked ophthalmologists with respect to the appearance of the far peripheral retina.
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UWFA acquisition and analysis A protocol was set for FA acquisition. UWFA was performed to obtain images of the far peripheral retina. All patients received an intravenous injection of 5 mL 10% sodium fluorescein through the antecubital vein. All eyes were dilated with tropicamide phenylephrine (Mydrin-P) to facilitate the capture of high quality images. For the UWFA and the 55° FA modules, the primary field was cente red on the fovea, and images of the peripheral retina were captured by instructing the patient to stare temporally, superotemporally, superiorly, superonasally, nasally, inferonassally, inferiorly, and inferotemporally to the extent as greatest as possible. For UWFA, images were captured in the early (10–30 s), mid (3–5 min), and late (10–15 min) phases,12 and at 20–30 min when the choroidal and retinal vessels were almost completely drained of fluorescein. For 55° FA, images were taken at the m id and late phases. The characteristics of the angiographic findings were analyzed. The far peripheral retina was defined as the retinal area anterior to the ampullae of the vortex veins and posterior to the ora serrata.5 A montage was created using images taken at different gaze angles to cover a retinal area as large as possible. The view fields of single shots and montages of both FA modules were calculated and analyzed in pixels using Adobe® Photoshop® C5 software (Adobe Systems Inc, CA, USA).
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Examination of ciliary body To determine whether the vessels of the far peripheral retina were affected by underlying inflammation, ultrasound biomicroscopy (UBM) was performed using a Suoer panoramic UBM instrument (Suoer Electonic Ltd, Model SW-3200L). The ciliary body was scanned perpendicularly in four meridians at 3 o'clock, 6 o'clock, 9 o'clock, and 12 o'clock when the patients were lying in the supine position under room light. Image description was performed by an ophthalmologist experienced in interpreting UBM images. The ciliary body thickness (CBT) was measured at 3 mm (CBT1) and 2 mm (CBT2) posterior to the scleral spur (Figure 3) using the Image J program (version 1.49, National Institutes of Health, Washington, DC). The measurements were performed in triplicate. The average of the measurements in four meridians was used for statistical comparison.
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Statistical analysis All data were analyzed using IBM SPSS Statistics version 20.0 (IBM Corporation, New York, USA). The paired-t test was used to compare the differences in fundal view fields obtained using UWFA and 55° FA. The chi-square test was used to compare the distribution of gender among the groups. One-way ANOVA was used to test the differences of CBT, age, and refractive error among the groups. The Scheffe test was used for pairwise comparison of CBT1 and refractive error across the three groups. The Dunnett T3 test was used for pairwise comparison of CBT2 across the three groups. A P value less than .05 was considered statistically significant.
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RESULTS During the 15-month study period, 101 eyes of 61 consecutive patients aged 15–65 years (average, 41 years) were enrolled with a female to male ratio of 0.97. The fundal fields obtained using the Heidelberg ultra-widefield lens in a single shot and in montage images were compared with those acquired using the Heidelberg conventional 55° lens (Figure 1). In an exploratory analysis of a subset of the study eyes (n = 10), the area of a single image and montage images captured by the Heidelberg Spectralis ultra-widefield lens versus the conventional 55° lens was 461305 ± 380 vs 142382 ± 1396 pixels (P = 0.000); and 1068375 ± 25606 vs 830421 ± 17967 pixels (P = 0.000), respectively. A single UWFA image captured 3.24× (range 3.19– 3.29×) the area captured by a single 55° FA image, and an UWFA montage image captured 1.29× (range 1.21–1.34×) the area captured by a 55° montage image. An analysis of the appearance of the far peripheral retina in the UWFA images revealed three different signs (Figure 2): a granular background fluorescence, mottled fluorescent band, and vascular leakage. The background fluorescence circling the far peripheral retina was slightly stronger than that of the posterior retina. The granular background fluorescence appeared early in the angiography and increased in intensity, coinciding with dye filling and increasing in the choroid. It showed no leakage in the late phase and faded out as the choroid was emptied of dye at the end of angiography. The mottled fluorescent band, a band with a diameter of 0.5-1 disc and unevenly distributed fluorescence, appeared at the far peripheral retina adjacent to the ora serrata. It consisted of hyperfluorescent and hypofluorescent components, and the hyperfluorescent component was dominant. The hyperfluorescent component appeared early in the angiography, increased in intensity as dye concentration in the choroid increased (window defect), and stained with fluorescein in the late phase and remained uniform in size throughout the angiogram without any leakage. Vascular leakage observed at the far peripheral retina showed fluffy fluorescence in the late phase of UWFA. Signs of the granular background fluorescence, mottled fluorescent band, and vascular leakage can occur simultaneously or separately. Dye leakage on fluorescein angiography are usually considered abnormal, since normal retinal blood vessels are impermeable to dye leakage.12 Therefore, based on the different combinations of these signs and our knowledge, the studied eyes were divided into three groups (Table 1). The eyes with peripheral vascular leakage were grouped separately as group 3. The eyes free of peripheral vascular leakage but with the mottled fluorescent band were divided into group 2, and the eyes with only granular background fluorescence were left
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for group 1. There were no significant differences among the three groups in terms of age, gender and refractive error (Table 2). In this study, 101 of 101 (100%) eyes had the granular background fluorescence, 44 of 101 (43.6%) eyes had the mottled fluorescent band, and 20 of 101 (19.8%) eyes had vascular leakage in the far peripheral retina. The prevalence of the granular background fluorescence, mottled fluorescent band, and vascular leakage in eyes with different diagnoses (floaters in the studied eyes, RVO and CSC in the fellow eyes) were listed in Table 3. All eyes in group 3 underwent UBM examination of the ciliary body to detect potential inflammation, which indicates underlying intermediate uveitis. Given that the eyes with granular background fluorescence and mottled fluorescent band lacked signs of inflammation and had no indication for UBM examination, only 40% of the eyes in both group 1 (18 eyes) and group 2 (15 eyes) were selected randomly for UBM examination to avoid additional costs. With UBM, swelling and exudates of the ciliary bodies were observed in group 3, but not in groups 1 and 2. Consistent with the observation, the mean CBT1 of group 3 was greater than that of group 1 and group 2 (0.315 ± 0.037 mm, 95%CI [0.298, 0.332], vs. 0.240 ± 0.019 mm, 95%CI [0.230, 0.249], vs. 0.251 ± 0.030 mm, 95%CI [0.234, 0.267], P = .000), while the mean CBT1 of group 1 and group 2 showed no difference (P = .575). Similarly, the mean CBT2 of group 3 was greater than that of group 1 and group 2 (0.571 ± 0.084 mm, 95%CI [0.532, 0.611], vs. 0.375 ± 0.051 mm, 95%CI [0.350, 0.400], vs. 0.410 ± 0.050 mm, 95%CI [0.382, 0.438], P = .000), while the mean CBT2 of group 1 and group 2 showed no difference (P = .150) (Figure 3).
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DISCUSSION In this study, we found that the retinal area captured by UWFA was larger than that captured by the 55° FA for both single images (3.24 ×) and montage images (1.29×). UWFA was superior in showing the far peripheral retina, especially in the nasal and inferior quadrants, which were difficult to image using 55° FA. Therefore, UWFA was the optimal choice for imaging the far peripheral retina of patients. In the UWFA images, granular background fluorescence was seen in all studied eyes (100%). Its characteristic fluorescence pattern resembles transmitted fluorescence (pigment epithelial window defect), an accentuation of the visibility of normal choroidal fluorescence. The band appeared early in angiography, showed no leakage in the late phase, and faded as the choroid was emptied of dye, which is consistent with the manifestation of transmitted fluorescence. It has been reported that retinal pigment epithelial (RPE) cell density decreased significantly from the posterior (4,220 ± 727 cells/mm2) to the peripheral (1,600 ± 411 cells/mm2) retina.13 This could well explain the existence of the granular background fluorescence at the far peripheral retina. When the pigment epithelial cell layer in the periphery is less pigmented owing to the reduced cell density, the staining of Bruch’s membrane, the choroid, and sclera may become more obvious. Therefore, the granular background fluorescence might be a normal sign at the peripheral retina, and might be caused by the absence of or reduction in pigmentation at that site. A mottled fluorescent band at the far peripheral retina next to the ora serrata was observed in a large percentage of the studied eyes (43.6%). For the mottled fluorescent
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band in the eyes of group 2 showed no signs of fluorescein leakage by UWFA and also showed no signs of swelling or exudates by UBM, the mottled fluorescent band was likely not associated with inflammation and might also be a normal sign at the far peripheral retina. We speculated that it might be caused by unevenly distributed pigment in RPE cells because the anatomies of the autopsied eyes have revealed that the RPE cells at the region of ora serrata are irregular and amorphous with melanin granules clump together in a few cells and disappear from others.14 Therefore, the hyperfluorescent component might be caused by an attenuation or absence of pigmentation, while the hypofluorescent component might correspond to the site where the amount of pigment increased. The vascular leakage was detected in 19.8% of the studied eyes, not as frequently observed as the other two signs. Generally, peripheral vascular leakage is associated with inflammation, developmental variation, traction on retinal vessels, diabetic retinopathy and pathologic myopia.5, 17-19 However, the leakage may not stem from developmental variation, since the vascular terminus in all eyes showed normal configuration and distribution without increased ramifications or straightening of peripheral vessels. Also, the vascular leakage could not be resulted from traction on retinal vessels, because no peripheral degeneration or retinal holes were seen. The eyes in our study were also free of diabetic retinopathy and pathologic myopia. In addition, the ciliary body thickness of group 3 (with vascular leakage) was increased when compared to the other two groups. Although the CBT has been reported to increase with increasing myopic refractive error,20 the refractive error in our study showed no difference among the three groups. Thus, we considered that the increased CBT as well as the peripheral vascular leakage may be signs of inflammation. Intermediate uveitis is the most likely candidate of the inflammation, because all eyes with peripheral vascular leakage in this study had floaters (Table 3). Vasculitis and floaters are common manifestations in intermediate uveitis, which are seen in 19% to 89.2%21-23 and 61%24 of the intermediate uveitis respectively. Moreover, both active and inactive intermediate uveitis can have peripheral vascular leakage.25 Therefore, we speculated that the leaking vessels indicated intermediate uveitis in this study. Additionally, since a relatively large percentage (25.0%) of eyes with floaters has vascular leakage, greater attention should be paid to eyes with floaters. We suggest that patients who are suffering from persistent, vision-impairing and unexplained floaters undergo UBM and fluorescein angiography. The limitations of this study were as follows. Only a single time point was studied for each patient. Thus, data regarding the stability or progression of the studied signs were not available. Long-term follow-ups are required to determine the nature of those signs on UWFA images observed in our study. Of course, our studied eyes were not perfectly normal eyes. The studied “normal” eyes were eyes with floaters or the contralateral eyes of CSC or RVO without any ocular pathologic findings in the regular examinations, because FA is an invasive examination and it will be against ethics to perform FA on completely normal eyes. In summary, UWFA provided substantial views of the far peripheral retina. The normal far peripheral retina has granular background fluorescence, with or without a mottled fluorescent band. A few “normal eyes” by regular examination could actually be abnormal, showing vascular leakage in the far peripheral retina by UWFA and
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inflammation of the ciliary body by UBM. Patients with persistent, vision-impairing and unexplained floaters should be scheduled to follow-up visits and monitored for progression with future eye examinations.
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ACKNOWLEDGEMENT FUNDING/SUPPORT: This work was supported by grants from the National Key Basic Research Program of China (973 Program: 2013CB967000) and the National Natural Science Foundation of China to YAN LUO (81371020). The funding organization had no role in the design or conduct of this research.
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OTHER ACKNOWLEDGMENTS: None.
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FINANCIAL DISCLOSURES: All authors have no financial disclosures.
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exudative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol. doi: 10.1007/s00417016-3415-x. 2016.07.14. 19. Oliver SC, Schwartz SD. Peripheral vessel leakage (PVL): a new angiographic finding in diabetic retinopathy identified with ultra wide-field fluorescein angiography. Semin Ophthalmol 2010;25(1-2):27-33. 20. Oliveira C, Tello C, Liebmann JM, Ritch R. Ciliary body thickness increases with increasing axial myopia. Am J Ophthalmol 2005;140(2):324-325. 21. Raja SC, Jabs DA, Dunn JP, et al. Pars planitis: clinical features and class II HLA associations. Ophthalmology 1999;106(3):594-599. 22. Romero R, Peralta J, Sendagorta E, Abelairas J. Pars planitis in children: epidemiologic, clinical, and therapeutic characteristics. J Pediatr Ophthalmol Strabismus 2007;44(5):288-293. 23. Arellanes-Garcia L, Navarro-Lopez L, Recillas-Gispert C. Pars planitis in the Mexican Mestizo population: ocular findings, treatment, and visual outcome. Ocul Immunol Inflamm 2003;11(1):53-60. 24. Ozdal PC, Berker N, Tugal-Tutkun I. Pars Planitis: epidemiology, clinical characteristics, management and visual prognosis. J Ophthalmic Vis Res 2015;10(4):469-480. 25. Gurlu VP, Alimgil ML, Esgin H. Fluorescein angiographic findings in cases with intermediate uveitis in the inactive phase. Can J Ophthalmol 2007;42(1):107-109.
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Figure legends
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FIGURE 1. Single-shot and montage images obtained using ultra-widefield fluorescein angiography and 55° fluorescein angiography. Non-steered posterior shots of single images obtained using 55°fluorescein angiography (FA) (Left) and ultra-widefield fluorescein angiography (UWFA) (Middle left) are shown. (Middle right) A montage image obtained using 55° FA is shown with the dotted border outlining the total retinal area. (Right) A montage image obtained using UWFA is shown with the solid circle outlining the total retinal area. The dotted line refers to the retinal areas shown in the images left to it. A single UWFA image captured 3.24× (range 3.19–3.29×) the area captured by a single 55° FA image, and a UWFA montage photograph captured 1.29× (range 1.21–1.34×) the area captured by a 55° montage photograph.
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FIGURE 2. The findings of ultra-widefield fluorescein angiography at far peripheral retina. (First panel) show the ultra-widefield fluorescein angiography (UWFA) images of an eye with granular background fluorescence (see asterisks), without mottled florescent band and vascular leakage. The granular background fluorescence emerged in the early phase (First panel, left), increased in intensity in the mid phase (First panel, middle left), showed no leakage in the late phase (First panel, middle right), and faded out gradually (First panel, right). (Second panel) show the UWFA images of an eye with mottled florescent band (see arrowheads). The hyperfluorescent component of the mottled florescent band appeared at the far peripheral retina adjacent to ora serrata (see arrows) in the early phase (Second panel, left), became more obvious in the mid phase (Second panel, middle left), and was stained in the late phase (Second panel, middle right and right). (Second panel, middle left) In the magnified image, the mottled florescent band is marked out with dotted lines. (Third panel) show the UWFA images of an eye with vascular leakage. Dye leaked from the vessels of the peripheral retina in the early phase (Third panel, left), became very intensive in the mid phase (Third panel, middle left), and gradually appeared fuzzy in the late phase (Third panel, middle right and right). The inset of the lower right/left corner shows a magnified version of the portion of the image encapsulated by the rectangle. FIGURE 3. Measurement of ciliary body thickness. The ultrasound biomicroscopy images (Top left from group 2 and Top right from group 3) show the measurement of ciliary body thickness (CBT). The dotted line starts at the scleral spur (S) and extends posteriorly, intersecting the inner surface of the sclera. CBT was measured perpendicular to the dotted line at 3 mm (CBT1) and 2 mm (CBT2) posterior to the scleral spur (S). (Bottom left) The mean CBT1 of the eyes with vascular leakage in group 3 were significantly larger than that of the eyes without vascular leakage in groups 1 and 2. The mean CBT1 of groups 1 and 2 showed no difference. (Bottom right) Similarly, the mean CBT2 of group 3 were larger than that of groups 1 and 2, while the mean CBT2 of groups 1 and 2 showed no difference.
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TABLE 1. Grouping of all studied eyes by the findings of ultra-widefield fluorescein angiography GB MB VL Number of eyes (%) Group 1 + – – 44 (43.6) Group 2 + + – 37 (36.6) Group 3 + +/– + 20 (19.8) GB: granular background fluorescence; MB: mottled fluorescent band; VL: vascular leakage; +: Exist; –: Non-exist.
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TABLE 2. Comparison of basic profiles among three groups Group1 Group2 Group3 P VL- MBVL- MB+ VL+ Value Number of patients (eyes) 27 (44) 24 (37) 10 (20) Number of female (%) 12 (44.4) 13 (54.2) 5 (50.0) .785a Age, y old, mean ± SD, 43 ± 15 42 ± 14 36 ± 15 .464b 95% CI, (37, 48) (36,48) (26,47) range 16-65 15-64 19-60 RE, D, mean ± SD, -0.213 ± 1.224 -0.135 ± 1.100 -0.800 ± 1.271 .112b 95% CI, (-0.585, 0.159) (-0.502, 0.232) (-1.395, -0.205) range -2.750 to +2.875 -2.750 to +1.750 -2.750 to +1.250 MB: mottled fluorescent band; VL: vascular leakage; RE: refractive error; a Chi-square test; b One-way ANOVA. Refractive error expressed as spherical equivalent in diopters.
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TABLE 3. Prevalence of granular background fluorescence, mottled fluorescent band and vascular leakage in eyes with different diagnoses No. of No. of eyes No. of eyes No. of eyes Diagnoses eyes with GB with MB with VL Floaters in the studied eye 80 80 (100%) 33 (41.3%) 20 (25.0%) RVO in the fellow eye 12 12 (100%) 7 (58.3%) 0 (0%) 9 9 (100%) 4 (44.4%) 0 (0%) CSC in the fellow eye Total 101 101 (100%) 44 (43.6%) 20 (19.8%) GB: granular background fluorescence; MB: mottled fluorescent band; VL: vascular leakage; RVO: retinal vein occlusion; CSC: central serous chorioretinopathy.
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S0002-9394(16)30480-9
DOI:
10.1016/j.ajo.2016.09.024
Reference:
AJOPHT 9906
To appear in:
American Journal of Ophthalmology
Received Date: 17 May 2016 Revised Date:
17 September 2016
Accepted Date: 21 September 2016
Please cite this article as: Lu J, Mai G, Luo Y, Li M, Cao D, Wang X, Yan H, Sadda SR, Lu L, Appearance of far peripheral retina in normal eyes by ultra-widefield fluorescein angiography, American Journal of Ophthalmology (2016), doi: 10.1016/j.ajo.2016.09.024. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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PURPOSE: To characterize the appearance of the far peripheral retina of normal eyes using ultra-widefield fluorescein angiography (UWFA). DESIGN: Cross-sectional study. METHODS: This study enrolled 101 eyes with best corrected visual acuity ≥ 20/20, refractive error < 3.00D, and without visible retinal pathologic changes under a slit lamp–based condensing lens. The far peripheral retina was detected by UWFA. Ciliary body thickness (CBT) at 3 mm (CBT1) and 2 mm (CBT2) posterior to the scleral spur was measured by ultrasound biomicroscopy. RESULTS: In the far peripheral retina, granular background fluorescence (GB) appeared in all eyes (100%), a mottled fluorescent band (MB) appeared in 44 (43.6%) eyes, and retinal vascular leakage (VL) appeared in 20 (19.8%) eyes. According to peripheral angiographic findings, the eyes were allocated into three groups: group 1 (MB- and VL-), group 2 (MB+ and VL-), and group 3 (MB-/+ and VL+). Ultrasound biomicroscopy showed ciliary body edema and exudates in group 3. The mean CBT1 (mm) and CBT2 (mm) of group 3 were greater than those of group 1 and group 2 (0.315 ± 0.037 vs. 0.240 ± 0.019 vs. 0.251 ± 0.030; 0.571 ± 0.084 vs. 0.375 ± 0.051 vs. 0.410 ± 0.050, P = .000 for both CBT1 and CBT2). The mean CBT1 and CBT2 showed no difference between group 1 and group 2 (P = .575 for CBT1; P = .150 for CBT2). CONCLUSIONS: Normal peripheral retinas generally show granular background fluorescence, with or without a mottled fluorescent band.
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Appearance of far peripheral retina in normal eyes by ultra-widefield fluorescein angiography Jing Lu1, Guiying Mai1, Yan Luo1, Mei Li1, Di Cao1, Xiao Wang1, Hong Yan1, SriniVas R. Sadda2, Lin Lu1
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1. State Key Laboratory of Ophthalmology, Image Reading Center, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China 2. Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California, USA
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Corresponding author: Lin Lu, State Key Laboratory of Ophthalmology, Image Reading Center, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China; phone: +86 13809773029; fax: 86-20-87335931; e-mail: [email protected]
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Short title: Peripheral retina by ultra-widefield fluorescein angiography
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Fundus fluorescein angiography (FA) has been used in pathophysiological evaluation of the retina and the choroid for more than 50 years.1 As the traditional fundus camera for FA can only offer a 30–60° view field of the fundus in a single shot, the seven-standard field protocol and the nine-field protocol have been developed to increase the view field of FA.2, 3 However, they are technically challenging for both patients and photographers, and fail to image the far peripheral retina. The subsequent application of a confocal scanning laser ophthalmoscope with a Staurenghi contact lens expands the viewing capability to a 150° view field, while its contact nature makes it less preferable in clinical application. The advent of the noncontact Optos C200 MA ultra-widefield retinal imaging system (Optos PLC, Dunfermline, Scotland, UK) makes it possible to observe the far peripheral retina via FA imaging in a variety of fundus diseases.4, 5 The Optos system is convenient to operate with extremely widefield visualization, and its newly commercial device has established a built-in stereographic projection software to reduce distortion.6 More recently, Heidelberg Engineering (Heidelberg, Germany) has developed a noncontact ultra-widefield fluorescein angiography (UWFA) imaging module that captures a 102° view field of the fundus in a singl e image.7 Although not used as widely as the Optos now, the ultra-widefield imaging lens offers the advantage of easy interchange with other existing lenses. It has been used successfully to inspect infants’ retinas intraoperatively.8 In our clinical practice, a mottled fluorescent band is frequently observed near the ora serrata in FA images. Whether this mottled fluorescent band is normal has not been confirmed yet. Only a few articles have been focused on the peripheral retina in normal eyes. One recent study has quantitatively evaluated the area of normal perfused retina in UWFA images.6 Another study has estimated the normal distance from vascular termini to ora serrata in children’s eyes.9 These studies has given detailed analysis of the perfusion and nonperfusion status of the peripheral retina, but still leaving other UWFA image features of the normal far peripheral retina undescribed. Therefore, our study aimed to investigate the appearance of the far peripheral retina in normal eyes by using the Heidelberg Spectralis UWFA imaging system. Such a description will provide valuable normative data for understanding pathologies of the far peripheral retina showing by FA images.
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METHODS This cross-sectional study was conducted from November 2014 to January 2016 at the fundus outpatient clinic in Zhongshan ophthalmic center. The study adhered to the tenets of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Zhongshan Ophthalmic Center, Sun Yat-Sen University (IRB approval number: 2016KYPJ029) and registered in ClinicalTrials.gov (ID number: NCT02856139). Informed consent for the study was obtained from each subject at the time of enrollment. Subjects All patients underwent a comprehensive eye examination including slit-lamp biomicroscopy, tonometry, refractive error measurements, and dilated fundus examination with a slit lamp–based +78 D or +90 D lens. Both eyes of patients with merely floaters or the fellow eyes of patients with retinal vein occlusion (RVO) or central serous chorioretinopathy (CSC) without any ocular pathologic findings in the above
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mentioned preliminary examinations were included in the study. Subjects with a history of ocular surgery, best-corrected visual acuity < 1.0 (20/20), refractive error ≥ 3.00 D, presence of ocular or systemic diseases, or opacity of refractive media which interfered with the peripheral retina image quality, were excluded from this study. Eyes were excluded if the quality of their FA images prevented reliable evaluation. The prevalence of symptomatic10 and asymptomatic floaters11 are fairly common in the general population and floaters cannot be considered abnormal when lacking other pathologic findings. Therefore, the eyes with floaters but without other pathologic findings in our study were set as “normal eyes” to investigate the appearance of the far peripheral retina. Demographic and clinical data such as age, gender, and reasons for undergoing FA were collected. All fundus examinations including FA were evaluated independently by two masked ophthalmologists with respect to the appearance of the far peripheral retina.
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UWFA acquisition and analysis A protocol was set for FA acquisition. UWFA was performed to obtain images of the far peripheral retina. All patients received an intravenous injection of 5 mL 10% sodium fluorescein through the antecubital vein. All eyes were dilated with tropicamide phenylephrine (Mydrin-P) to facilitate the capture of high quality images. For the UWFA and the 55° FA modules, the primary field was cente red on the fovea, and images of the peripheral retina were captured by instructing the patient to stare temporally, superotemporally, superiorly, superonasally, nasally, inferonassally, inferiorly, and inferotemporally to the extent as greatest as possible. For UWFA, images were captured in the early (10–30 s), mid (3–5 min), and late (10–15 min) phases,12 and at 20–30 min when the choroidal and retinal vessels were almost completely drained of fluorescein. For 55° FA, images were taken at the m id and late phases. The characteristics of the angiographic findings were analyzed. The far peripheral retina was defined as the retinal area anterior to the ampullae of the vortex veins and posterior to the ora serrata.5 A montage was created using images taken at different gaze angles to cover a retinal area as large as possible. The view fields of single shots and montages of both FA modules were calculated and analyzed in pixels using Adobe® Photoshop® C5 software (Adobe Systems Inc, CA, USA).
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Examination of ciliary body To determine whether the vessels of the far peripheral retina were affected by underlying inflammation, ultrasound biomicroscopy (UBM) was performed using a Suoer panoramic UBM instrument (Suoer Electonic Ltd, Model SW-3200L). The ciliary body was scanned perpendicularly in four meridians at 3 o'clock, 6 o'clock, 9 o'clock, and 12 o'clock when the patients were lying in the supine position under room light. Image description was performed by an ophthalmologist experienced in interpreting UBM images. The ciliary body thickness (CBT) was measured at 3 mm (CBT1) and 2 mm (CBT2) posterior to the scleral spur (Figure 3) using the Image J program (version 1.49, National Institutes of Health, Washington, DC). The measurements were performed in triplicate. The average of the measurements in four meridians was used for statistical comparison.
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Statistical analysis All data were analyzed using IBM SPSS Statistics version 20.0 (IBM Corporation, New York, USA). The paired-t test was used to compare the differences in fundal view fields obtained using UWFA and 55° FA. The chi-square test was used to compare the distribution of gender among the groups. One-way ANOVA was used to test the differences of CBT, age, and refractive error among the groups. The Scheffe test was used for pairwise comparison of CBT1 and refractive error across the three groups. The Dunnett T3 test was used for pairwise comparison of CBT2 across the three groups. A P value less than .05 was considered statistically significant.
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RESULTS During the 15-month study period, 101 eyes of 61 consecutive patients aged 15–65 years (average, 41 years) were enrolled with a female to male ratio of 0.97. The fundal fields obtained using the Heidelberg ultra-widefield lens in a single shot and in montage images were compared with those acquired using the Heidelberg conventional 55° lens (Figure 1). In an exploratory analysis of a subset of the study eyes (n = 10), the area of a single image and montage images captured by the Heidelberg Spectralis ultra-widefield lens versus the conventional 55° lens was 461305 ± 380 vs 142382 ± 1396 pixels (P = 0.000); and 1068375 ± 25606 vs 830421 ± 17967 pixels (P = 0.000), respectively. A single UWFA image captured 3.24× (range 3.19– 3.29×) the area captured by a single 55° FA image, and an UWFA montage image captured 1.29× (range 1.21–1.34×) the area captured by a 55° montage image. An analysis of the appearance of the far peripheral retina in the UWFA images revealed three different signs (Figure 2): a granular background fluorescence, mottled fluorescent band, and vascular leakage. The background fluorescence circling the far peripheral retina was slightly stronger than that of the posterior retina. The granular background fluorescence appeared early in the angiography and increased in intensity, coinciding with dye filling and increasing in the choroid. It showed no leakage in the late phase and faded out as the choroid was emptied of dye at the end of angiography. The mottled fluorescent band, a band with a diameter of 0.5-1 disc and unevenly distributed fluorescence, appeared at the far peripheral retina adjacent to the ora serrata. It consisted of hyperfluorescent and hypofluorescent components, and the hyperfluorescent component was dominant. The hyperfluorescent component appeared early in the angiography, increased in intensity as dye concentration in the choroid increased (window defect), and stained with fluorescein in the late phase and remained uniform in size throughout the angiogram without any leakage. Vascular leakage observed at the far peripheral retina showed fluffy fluorescence in the late phase of UWFA. Signs of the granular background fluorescence, mottled fluorescent band, and vascular leakage can occur simultaneously or separately. Dye leakage on fluorescein angiography are usually considered abnormal, since normal retinal blood vessels are impermeable to dye leakage.12 Therefore, based on the different combinations of these signs and our knowledge, the studied eyes were divided into three groups (Table 1). The eyes with peripheral vascular leakage were grouped separately as group 3. The eyes free of peripheral vascular leakage but with the mottled fluorescent band were divided into group 2, and the eyes with only granular background fluorescence were left
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for group 1. There were no significant differences among the three groups in terms of age, gender and refractive error (Table 2). In this study, 101 of 101 (100%) eyes had the granular background fluorescence, 44 of 101 (43.6%) eyes had the mottled fluorescent band, and 20 of 101 (19.8%) eyes had vascular leakage in the far peripheral retina. The prevalence of the granular background fluorescence, mottled fluorescent band, and vascular leakage in eyes with different diagnoses (floaters in the studied eyes, RVO and CSC in the fellow eyes) were listed in Table 3. All eyes in group 3 underwent UBM examination of the ciliary body to detect potential inflammation, which indicates underlying intermediate uveitis. Given that the eyes with granular background fluorescence and mottled fluorescent band lacked signs of inflammation and had no indication for UBM examination, only 40% of the eyes in both group 1 (18 eyes) and group 2 (15 eyes) were selected randomly for UBM examination to avoid additional costs. With UBM, swelling and exudates of the ciliary bodies were observed in group 3, but not in groups 1 and 2. Consistent with the observation, the mean CBT1 of group 3 was greater than that of group 1 and group 2 (0.315 ± 0.037 mm, 95%CI [0.298, 0.332], vs. 0.240 ± 0.019 mm, 95%CI [0.230, 0.249], vs. 0.251 ± 0.030 mm, 95%CI [0.234, 0.267], P = .000), while the mean CBT1 of group 1 and group 2 showed no difference (P = .575). Similarly, the mean CBT2 of group 3 was greater than that of group 1 and group 2 (0.571 ± 0.084 mm, 95%CI [0.532, 0.611], vs. 0.375 ± 0.051 mm, 95%CI [0.350, 0.400], vs. 0.410 ± 0.050 mm, 95%CI [0.382, 0.438], P = .000), while the mean CBT2 of group 1 and group 2 showed no difference (P = .150) (Figure 3).
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DISCUSSION In this study, we found that the retinal area captured by UWFA was larger than that captured by the 55° FA for both single images (3.24 ×) and montage images (1.29×). UWFA was superior in showing the far peripheral retina, especially in the nasal and inferior quadrants, which were difficult to image using 55° FA. Therefore, UWFA was the optimal choice for imaging the far peripheral retina of patients. In the UWFA images, granular background fluorescence was seen in all studied eyes (100%). Its characteristic fluorescence pattern resembles transmitted fluorescence (pigment epithelial window defect), an accentuation of the visibility of normal choroidal fluorescence. The band appeared early in angiography, showed no leakage in the late phase, and faded as the choroid was emptied of dye, which is consistent with the manifestation of transmitted fluorescence. It has been reported that retinal pigment epithelial (RPE) cell density decreased significantly from the posterior (4,220 ± 727 cells/mm2) to the peripheral (1,600 ± 411 cells/mm2) retina.13 This could well explain the existence of the granular background fluorescence at the far peripheral retina. When the pigment epithelial cell layer in the periphery is less pigmented owing to the reduced cell density, the staining of Bruch’s membrane, the choroid, and sclera may become more obvious. Therefore, the granular background fluorescence might be a normal sign at the peripheral retina, and might be caused by the absence of or reduction in pigmentation at that site. A mottled fluorescent band at the far peripheral retina next to the ora serrata was observed in a large percentage of the studied eyes (43.6%). For the mottled fluorescent
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band in the eyes of group 2 showed no signs of fluorescein leakage by UWFA and also showed no signs of swelling or exudates by UBM, the mottled fluorescent band was likely not associated with inflammation and might also be a normal sign at the far peripheral retina. We speculated that it might be caused by unevenly distributed pigment in RPE cells because the anatomies of the autopsied eyes have revealed that the RPE cells at the region of ora serrata are irregular and amorphous with melanin granules clump together in a few cells and disappear from others.14 Therefore, the hyperfluorescent component might be caused by an attenuation or absence of pigmentation, while the hypofluorescent component might correspond to the site where the amount of pigment increased. The vascular leakage was detected in 19.8% of the studied eyes, not as frequently observed as the other two signs. Generally, peripheral vascular leakage is associated with inflammation, developmental variation, traction on retinal vessels, diabetic retinopathy and pathologic myopia.5, 17-19 However, the leakage may not stem from developmental variation, since the vascular terminus in all eyes showed normal configuration and distribution without increased ramifications or straightening of peripheral vessels. Also, the vascular leakage could not be resulted from traction on retinal vessels, because no peripheral degeneration or retinal holes were seen. The eyes in our study were also free of diabetic retinopathy and pathologic myopia. In addition, the ciliary body thickness of group 3 (with vascular leakage) was increased when compared to the other two groups. Although the CBT has been reported to increase with increasing myopic refractive error,20 the refractive error in our study showed no difference among the three groups. Thus, we considered that the increased CBT as well as the peripheral vascular leakage may be signs of inflammation. Intermediate uveitis is the most likely candidate of the inflammation, because all eyes with peripheral vascular leakage in this study had floaters (Table 3). Vasculitis and floaters are common manifestations in intermediate uveitis, which are seen in 19% to 89.2%21-23 and 61%24 of the intermediate uveitis respectively. Moreover, both active and inactive intermediate uveitis can have peripheral vascular leakage.25 Therefore, we speculated that the leaking vessels indicated intermediate uveitis in this study. Additionally, since a relatively large percentage (25.0%) of eyes with floaters has vascular leakage, greater attention should be paid to eyes with floaters. We suggest that patients who are suffering from persistent, vision-impairing and unexplained floaters undergo UBM and fluorescein angiography. The limitations of this study were as follows. Only a single time point was studied for each patient. Thus, data regarding the stability or progression of the studied signs were not available. Long-term follow-ups are required to determine the nature of those signs on UWFA images observed in our study. Of course, our studied eyes were not perfectly normal eyes. The studied “normal” eyes were eyes with floaters or the contralateral eyes of CSC or RVO without any ocular pathologic findings in the regular examinations, because FA is an invasive examination and it will be against ethics to perform FA on completely normal eyes. In summary, UWFA provided substantial views of the far peripheral retina. The normal far peripheral retina has granular background fluorescence, with or without a mottled fluorescent band. A few “normal eyes” by regular examination could actually be abnormal, showing vascular leakage in the far peripheral retina by UWFA and
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inflammation of the ciliary body by UBM. Patients with persistent, vision-impairing and unexplained floaters should be scheduled to follow-up visits and monitored for progression with future eye examinations.
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ACKNOWLEDGEMENT FUNDING/SUPPORT: This work was supported by grants from the National Key Basic Research Program of China (973 Program: 2013CB967000) and the National Natural Science Foundation of China to YAN LUO (81371020). The funding organization had no role in the design or conduct of this research.
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OTHER ACKNOWLEDGMENTS: None.
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FINANCIAL DISCLOSURES: All authors have no financial disclosures.
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REFERENCES 1. Novotny HR, Alvis DL. A method of photographing fluorescence in circulating blood in the human retina. Circulation 1961;24(1):82-86. 2. Kim DY, Kim JG, Kim YJ, Joe SG, Lee JY. Ultra-widefield fluorescein angiographic findings in patients with recurrent vitreous hemorrhage after diabetic vitrectomy. Invest Ophthalmol Vis Sci 2014;55(11):7040-7046. 3. Nicholson BP, Nigam D, Miller D, et al. Comparison of wide-field fluorescein angiography and 9-field montage angiography in uveitis. Am J Ophthalmol 2014;157(3):673-677. 4. Karampelas M, Sim DA, Chu C, et al. Quantitative analysis of peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography. Am J Ophthalmol 2015;159(6):1161-1168. 5. Kaneko Y, Moriyama M, Hirahara S, Ogura Y, Ohno-Matsui K. Areas of nonperfusion in peripheral retina of eyes with pathologic myopia detected by ultra-widefield fluorescein angiography. Invest Ophthalmol Vis Sci 2014;55(3):1432-1439. 6. Singer M, Sagong M, van Hemert J, et al. Ultra-widefield Imaging of the Peripheral Retinal Vasculature in Normal Subjects. Ophthalmology 2016;123(5):1053-1059. 7. Witmer MT, Parlitsis G, Patel S, Kiss S. Comparison of ultra-widefield fluorescein angiography with the Heidelberg Spectralis noncontact ultra-widefield module versus the Optos Optomap. Clin Ophthalmol 2013;7:389-394. 8. Fung TH, Yusuf IH, Xue K, Smith LM, Patel CK. Heidelberg Spectralis ultra-widefield fundus fluorescein angiography in infants. Am J Ophthalmol 2015;159(1):78-84. 9. Blair MP, Shapiro MJ, Hartnett ME. Fluorescein angiography to estimate normal peripheral retinal nonperfusion in children. J AAPOS 2012;16(3):234-237. 10. Webb BF, Webb JR, Schroeder MC, North CS. Prevalence of vitreous floaters in a community sample of smartphone users. Int J Ophthalmol 2013;6(3):402-405. 11. Tassignon MJ, Ni Dhubhghaill S, Ruiz Hidalgo I, Rozema JJ. Subjective Grading of Subclinical Vitreous Floaters. Asia Pac J Ophthalmol (Phila) 2016;5(2):104-109. 12. Johnson RN, Fu AD, McDonald HR, et al. Fluorescein angiography: basic principles and interpretation. In: Ryan SJ, Sadda S, Hinton D, editors. Retina (5th ed). London: W.B. Saunders, 2013:14-16. 13. Panda-Jonas S, Jonas JB, Jakobczyk-Zmija M. Retinal pigment epithelial cell count, distribution, and correlations in normal human eyes. Am J Ophthalmol 1996;121(2):181189. 14. Zinn KM, Benjamin-Henkind JV. Retinal pigment epithelium. In: Jakobiec FA, editor. Ocular anatomy, embryology, and teratology. Philadelphia: Harper and Row, 1982:536. 15. O'Malley PF, Allen RA. Peripheral cystoid degeneration of the retina. Incidence and distribution in 1,000 autopsy eyes. Arch Ophthalmol 1967;77(6):769-776. 16. Rutnin U, Schepens CL. Fundus appearance in normal eyes. 3. Peripheral degenerations. Am J Ophthalmol 1967;64(6):1040-1062. 17. Karampelas M, Sim DA, Chu C, et al. Quantitative analysis of peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography. Am J Ophthalmol 2015;159(6):1161-1168. 18. Lyu J, Zhang Q, Wang SY, et al. Ultra-wide-field scanning laser ophthalmoscopy assists in the clinical detection and evaluation of asymptomatic early-stage familial
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exudative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol. doi: 10.1007/s00417016-3415-x. 2016.07.14. 19. Oliver SC, Schwartz SD. Peripheral vessel leakage (PVL): a new angiographic finding in diabetic retinopathy identified with ultra wide-field fluorescein angiography. Semin Ophthalmol 2010;25(1-2):27-33. 20. Oliveira C, Tello C, Liebmann JM, Ritch R. Ciliary body thickness increases with increasing axial myopia. Am J Ophthalmol 2005;140(2):324-325. 21. Raja SC, Jabs DA, Dunn JP, et al. Pars planitis: clinical features and class II HLA associations. Ophthalmology 1999;106(3):594-599. 22. Romero R, Peralta J, Sendagorta E, Abelairas J. Pars planitis in children: epidemiologic, clinical, and therapeutic characteristics. J Pediatr Ophthalmol Strabismus 2007;44(5):288-293. 23. Arellanes-Garcia L, Navarro-Lopez L, Recillas-Gispert C. Pars planitis in the Mexican Mestizo population: ocular findings, treatment, and visual outcome. Ocul Immunol Inflamm 2003;11(1):53-60. 24. Ozdal PC, Berker N, Tugal-Tutkun I. Pars Planitis: epidemiology, clinical characteristics, management and visual prognosis. J Ophthalmic Vis Res 2015;10(4):469-480. 25. Gurlu VP, Alimgil ML, Esgin H. Fluorescein angiographic findings in cases with intermediate uveitis in the inactive phase. Can J Ophthalmol 2007;42(1):107-109.
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Figure legends
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FIGURE 1. Single-shot and montage images obtained using ultra-widefield fluorescein angiography and 55° fluorescein angiography. Non-steered posterior shots of single images obtained using 55°fluorescein angiography (FA) (Left) and ultra-widefield fluorescein angiography (UWFA) (Middle left) are shown. (Middle right) A montage image obtained using 55° FA is shown with the dotted border outlining the total retinal area. (Right) A montage image obtained using UWFA is shown with the solid circle outlining the total retinal area. The dotted line refers to the retinal areas shown in the images left to it. A single UWFA image captured 3.24× (range 3.19–3.29×) the area captured by a single 55° FA image, and a UWFA montage photograph captured 1.29× (range 1.21–1.34×) the area captured by a 55° montage photograph.
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FIGURE 2. The findings of ultra-widefield fluorescein angiography at far peripheral retina. (First panel) show the ultra-widefield fluorescein angiography (UWFA) images of an eye with granular background fluorescence (see asterisks), without mottled florescent band and vascular leakage. The granular background fluorescence emerged in the early phase (First panel, left), increased in intensity in the mid phase (First panel, middle left), showed no leakage in the late phase (First panel, middle right), and faded out gradually (First panel, right). (Second panel) show the UWFA images of an eye with mottled florescent band (see arrowheads). The hyperfluorescent component of the mottled florescent band appeared at the far peripheral retina adjacent to ora serrata (see arrows) in the early phase (Second panel, left), became more obvious in the mid phase (Second panel, middle left), and was stained in the late phase (Second panel, middle right and right). (Second panel, middle left) In the magnified image, the mottled florescent band is marked out with dotted lines. (Third panel) show the UWFA images of an eye with vascular leakage. Dye leaked from the vessels of the peripheral retina in the early phase (Third panel, left), became very intensive in the mid phase (Third panel, middle left), and gradually appeared fuzzy in the late phase (Third panel, middle right and right). The inset of the lower right/left corner shows a magnified version of the portion of the image encapsulated by the rectangle. FIGURE 3. Measurement of ciliary body thickness. The ultrasound biomicroscopy images (Top left from group 2 and Top right from group 3) show the measurement of ciliary body thickness (CBT). The dotted line starts at the scleral spur (S) and extends posteriorly, intersecting the inner surface of the sclera. CBT was measured perpendicular to the dotted line at 3 mm (CBT1) and 2 mm (CBT2) posterior to the scleral spur (S). (Bottom left) The mean CBT1 of the eyes with vascular leakage in group 3 were significantly larger than that of the eyes without vascular leakage in groups 1 and 2. The mean CBT1 of groups 1 and 2 showed no difference. (Bottom right) Similarly, the mean CBT2 of group 3 were larger than that of groups 1 and 2, while the mean CBT2 of groups 1 and 2 showed no difference.
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TABLE 1. Grouping of all studied eyes by the findings of ultra-widefield fluorescein angiography GB MB VL Number of eyes (%) Group 1 + – – 44 (43.6) Group 2 + + – 37 (36.6) Group 3 + +/– + 20 (19.8) GB: granular background fluorescence; MB: mottled fluorescent band; VL: vascular leakage; +: Exist; –: Non-exist.
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TABLE 2. Comparison of basic profiles among three groups Group1 Group2 Group3 P VL- MBVL- MB+ VL+ Value Number of patients (eyes) 27 (44) 24 (37) 10 (20) Number of female (%) 12 (44.4) 13 (54.2) 5 (50.0) .785a Age, y old, mean ± SD, 43 ± 15 42 ± 14 36 ± 15 .464b 95% CI, (37, 48) (36,48) (26,47) range 16-65 15-64 19-60 RE, D, mean ± SD, -0.213 ± 1.224 -0.135 ± 1.100 -0.800 ± 1.271 .112b 95% CI, (-0.585, 0.159) (-0.502, 0.232) (-1.395, -0.205) range -2.750 to +2.875 -2.750 to +1.750 -2.750 to +1.250 MB: mottled fluorescent band; VL: vascular leakage; RE: refractive error; a Chi-square test; b One-way ANOVA. Refractive error expressed as spherical equivalent in diopters.
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TABLE 3. Prevalence of granular background fluorescence, mottled fluorescent band and vascular leakage in eyes with different diagnoses No. of No. of eyes No. of eyes No. of eyes Diagnoses eyes with GB with MB with VL Floaters in the studied eye 80 80 (100%) 33 (41.3%) 20 (25.0%) RVO in the fellow eye 12 12 (100%) 7 (58.3%) 0 (0%) 9 9 (100%) 4 (44.4%) 0 (0%) CSC in the fellow eye Total 101 101 (100%) 44 (43.6%) 20 (19.8%) GB: granular background fluorescence; MB: mottled fluorescent band; VL: vascular leakage; RVO: retinal vein occlusion; CSC: central serous chorioretinopathy.
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